Does Thyroid Peroxidase (TPO) antibody always rise with hypothyroidism?

Does Thyroid Peroxidase (TPO) Antibody Always Rise with Hypothyroidism?

No, TPO antibodies do not always rise with hypothyroidism, as hypothyroidism can occur due to various etiologies beyond autoimmune thyroiditis, including post-surgical or post-radioiodine treatment states where TPO antibodies may be absent.

Relationship Between TPO Antibodies and Hypothyroidism

TPO antibodies are primarily markers of autoimmune thyroid disease rather than hypothyroidism itself. According to clinical guidelines, the presence of anti-TPO antibodies:

• Identifies an autoimmune etiology for thyroid dysfunction 1
• Predicts a higher risk of developing overt hypothyroidism (4.3% per year vs 2.6% per year in antibody-negative individuals) 1
• Does not change the diagnosis of hypothyroidism, which is based on serum TSH measurements 1

Causes of Hypothyroidism Without Elevated TPO Antibodies

Several causes of hypothyroidism exist where TPO antibodies may be normal:

1. Iatrogenic causes:

   • Post-thyroidectomy
   • Post-radioiodine treatment
   • Medication-induced (amiodarone, lithium)

2. Central hypothyroidism (pituitary or hypothalamic dysfunction)

3. Iodine deficiency or excess

4. Congenital hypothyroidism

5. Infiltrative disorders affecting the thyroid

Prevalence of TPO Antibodies in Hypothyroidism

While TPO antibodies are common in hypothyroidism, they are not universal:

• In autoimmune hypothyroidism (Hashimoto's thyroiditis), approximately 96% of patients have positive anti-TPO antibodies when using a cut-off of 200 units/ml 2
• However, this means that even in autoimmune hypothyroidism, approximately 4% of patients may not have detectable TPO antibodies

Clinical Significance of TPO Antibodies

TPO antibodies have important clinical implications even when thyroid function is normal:

• They correlate with the degree of lymphocytic infiltration in euthyroid subjects 3
• Even within the normal range for TSH, TPO antibody titers correlate with TSH levels 3
• The presence of TPO antibodies >500 IU/ml indicates a moderately increased risk for developing hypothyroidism 4
• In the Whickham survey, the annual risk of developing hypothyroidism in TPO-positive women with normal TSH levels was 2.1% 3

Diagnostic Approach

When evaluating thyroid function:

1. Diagnosis of hypothyroidism is based on elevated TSH with low or normal free T4, not on TPO antibody status 1
2. TPO antibody testing can help determine etiology and risk of progression:
   • Positive TPO antibodies suggest autoimmune thyroiditis
   • Negative TPO antibodies should prompt consideration of other causes

Common Pitfalls

1. Assuming all hypothyroidism is autoimmune: Not all cases of hypothyroidism are caused by autoimmune thyroiditis, and therefore not all will have elevated TPO antibodies.

2. Over-reliance on TPO antibodies for diagnosis: The diagnosis of hypothyroidism should be based on TSH and free T4 levels, not TPO antibody status.

3. Treating based on TPO antibodies alone: Current guidelines do not support treating patients with normal thyroid function tests who have elevated TPO antibodies 5.

4. Ignoring TPO antibodies in euthyroid patients: The presence of TPO antibodies in euthyroid individuals indicates increased risk for future hypothyroidism and may warrant closer monitoring 3.

In summary, while TPO antibodies are frequently present in hypothyroidism (particularly autoimmune hypothyroidism), they are not a universal finding in all cases of hypothyroidism, and their presence or absence does not change the diagnostic criteria for hypothyroidism.